Work on this project has demonstrated that value-based decision making requires both the OFC and the amygdala for normal operations. We use a decision-making task that requires subjects to make choices associated with rewards of different value. In this task, the value of rewards is varied by prior consumption of a food item that serves as a reward. Eating a certain kind of food leads to a selective satiation that temporarily decreases the value of that food. We found that the OFC and the amygdala both play a necessary, causal role in the rapid updating of valuations, based on current biological needs. Our previous work had emphasized the valuation of objects, but traditional psychological theory has focused on the valuation of actions rather than of objects. Specifically, the learning-theory literature stresses the valuation of actions to guide goal-directed behavior. To investigate the role of the amygdala in updating the valuation of actions, we designed a novel task. Subjects were trained to perform two different actions on a touch screen. Repetitive tapping produced one food; constant holding produced a different food. Subjects were fed one of the foods to satiety, which lowered its value. Control subjects showed a reduction in the action associated with obtaining the devalued food. This result, called the devaluation effect, is a hallmark of goal-directed behavior. Subjects with bilateral lesions of either OFC or the amygdala exhibited significantly reduced devaluation effects. These results show that both OFC and the amygdala play an essential, causal role in goal-directed behavior that depend on the valuation of actions, which complements our earlier findings on the valuation of objects. Notably, these findings challenge the idea that the OFC and MFC are specialized for object- and action valuation, respectively. They also confirm our previous results showing that the amygdala plays an important role in positive valuations and emotions, which balances the overemphasis in the literature on negative valuations and emotions. To build on these findings, and to investigate whether the amygdala and either the OFC or MFC interact to guide goal-directed behavior, we are currently examining the effect of surgical crossed-disconnections of the amygdala and the frontal lobe on the performance of the same test of goal directed behavior described above. We are studying both amygdala-MFC and amygdala-OFC interactions. Our preliminary data suggest that functional interaction of the amygdala with OFC, but not MFC, is essential for goal-directed behavior. For decades, both clinical and experimental work on the OFC have been dominated by the idea that it regulates emotion and enhances behavioral flexibility through inhibitory control. In support of this idea, profoundly altered emotion regulation is a hallmark of damage or dysfunction within OFC. In addition, OFC damage yields an impairment in the ability to rapidly alter object-reward associations, as assessed in the object reversal learning task, a finding taken to support the role of OFC in inhibitory control. This influential result has been replicated many times, but our research has shown that the interpretation of this finding has been incorrect. Our earlier work showed that subtotal fiber-sparing, excitotoxic lesions of OFC failed to produce the expected changes in behavioral flexibility and emotion regulation. This failure, however, may have resulted because complete OFC lesions are needed to produce the classic behavioral effects. Alternatively, however, the effects of OFC damage may have depended on inadvertent damage to fiber tracts running near or through OFC and not on the function of OFC per se. To examine these possibilities we assessed subjects with excitotoxic lesions of OFC on two tests of inhibitory control (object reversal learning and snake fear) and one of updating object valuations, like the tasks described above. Unlike aspirations lesions of OFC, damage limited to cells in this area, but sparing fibers, did not affect either behavioral flexibility, as measured by object reversal learning, or emotion regulation, as reflected in measures of snake fear. These complete, excitotoxic lesions of OFC did, however, cause the same impairment in updating valuations that follows aspiration lesions of the same area. In a follow-up experiment, aspiration of a narrow strip of cortex in the posterior OFC reproduced the often-replicated impairments in object reversal learning and the blunting of snake fear caused by aspiration lesions of the entire OFC. Taken together, these findings show that inadvertent damage to fibers passing near or through OFC causes the impairments in behavioral flexibility and emotion regulation typically attributed to OFC. The results also support the idea that the OFC performs a more specific function in reward-guided behavior and emotion than currently thought, and indicate that this function includes the updating of object valuations according to current motivational states. We can reject the influential idea that the primary function of the OFC involves inhibitory control. Although loss of neurons in OFC per se is not responsible for the impairment in reversal learning or the dysregulation of snake fear, loss of neurons in some other parts of the frontal cortex presumably causes these classic results. Future studies will need to identify the specific frontal areas that mediate behavioral flexibility and emotion regulation. We have also studied the contribution of the amygdala to emotional processes. Learning, memory, attention and perception are all influenced by amygdala activity when subjects are perceiving and encoding emotional stimuli. Lesion studies have shown that the perception of emotional content of stimuli is affected by amygdala damage. For example, previous work on this project has shown that amygdala damage disrupts snake fear. Nevertheless, there is little work that assesses the contribution of the amygdala to social behavior in a rigorous manner. Accordingly, we examined the role of the amygdala in an attention task with social and nonsocial stimuli. Subjects with bilateral amygdala damage and control subjects performed an attention task in which they viewed social stimuli (pictures of a socially relevant portion of a face, such as the eye or mouth) or nonsocial stimuli (such as a geometrical shape). After viewing the stimuli, the subjects made a saccade to a visible target. Control subjects showed a significantly higher latency to initiate a saccade when presented with a social stimulus compared to a nonsocial one. By contrast, subjects with amygdala lesions showed the same latency to saccade for social and nonsocial stimuli, thereby indicating a lack of attention to social cues. These data show that the amygdala plays a crucial role in attending to and recognizing social cues.